DNA fragmentation in spermatozoa: a historical review

Abstract

SummarySperm DNA Fragmentation has been extensively studied for more than a decade. In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the DNA was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated. In the seventies, the impact of induced DNA damage was investigated. In the 1980s the concept of sperm DNA fragmentation as related to infertility was introduced as well as the first DNA fragmentation test: the Sperm Chromatin Structure Assay (SCSA). The terminal deoxynucleotidyl transferase nick end labelling (TUNEL) test followed by others was introduced in the nineties. The association between DNA fragmentation in spermatozoa and pregnancy loss has been extensively investigated spurring the need for a therapeutic tool for these patients. This gave rise to an increased interest in the aetiology of DNA damage. The present decade continues within this research area. Some of the more novel methods recently submerging are sorting of cells with increased DNA fragmentation and hyaluronic acid (HA) binding techniques. The clinical value of these tests remains to be elucidated. In spite of half a century of research within the area, this analysis is not routinely implemented into the fertility clinics. The underlying causes are multiple. The abundance of methods has impeded the need for a clinical significant threshold. One of the most promising methods was commercialized in 2005 and has been reserved for larger licensed laboratories. Myriads of reviews and meta‐analyses on studies using different assays for analysis of DNA fragmentation, different clinical Artificial Reproductive Treatments (ART), different definitions of successful ART outcome and small patient cohorts have been published. Although the area of DNA fragmentation in spermatozoa is highly relevant in the fertility clinics, the need for further studies focusing on standardization of the methods and clinical implementation persists.

A global view of the pathophysiology of varicocele

“…Morphologically abnormal spermatozoa are more likely to have poor chromatin compaction, but a morphologically normal spermatozoon may also have poor chromatin compaction (Boitrelle et al, 2015). The effect of sperm DNA damage on pregnancy, embryonic development, and offspring health is a concern, and sperm DNA compaction/fragmentation can be additional diagnostic and prognostic markers for subfertile men with varicocele (Boitrelle et al, 2015;Cho et al, 2016); and according to the current data, standardization and clinical implementation of sperm DNA fragmentation tests are still recommended (Rex et al, 2017).…”

Investigating the relationship between BRCA1 and BRCA2 genes methylation profile and sperm DNA fragmentation in infertile men

“…Semen parameters such as sperm morphology and motility have been negatively correlated with increased DNA fragmentation (Evgeni, Charalabopoulos, & Asimakopoulos, ). Since conventional semen analysis is insufficient to explain all male infertility cases, testing for sDF has been proposed to be integrated in routine evaluation of male infertility, especially before assisted reproductive technology (ART; Rex, Aagaard, & Fedder, ). Although this is not yet a universally accepted procedure, application of the sDF test is considered to be meaningful and recommended in the latest guidelines published by both American and European Associations of Urology, particularly for the cases of idiopathic infertility with recurrent failure of ART and clinical varicocele (Cho & Agarwal, ).…”

“…Among different theories used to explain increased sDF in infertile men, abortive apoptosis, defective chromatin packaging and increased ROS production are considered as the most prominent ones (Tamburrino et al, ). These theories are not necessarily mutually exclusive, as defects in protamination may render DNA more susceptible to damage by ROS (Rex et al, ). Additionally, defects in antioxidant enzymes and DNA repair mechanisms have also been suggested to contribute to increased sDF and exacerbate the overall situation (Evgeni et al, ).…”

Human sperm DNA damage has an effect on immunological interaction between spermatozoa and fallopian tube

“…Sperm DNA fragmentation (SDF) is a parameter in male infertility evaluation. The major contributors of sperm DNA damage are oxidative stress, apoptosis, and chromatin remodeling (Fraczek et al ., ; Leach et al ., ; Rex et al ., ). High SDF has been associated with infertility and recurrent pregnancy loss (Bisht et al ., ), but this mechanism is not well recognized.…”